Cognitive Enhancement Therapy for Adult Autism Spectrum Disorder

 描述（由申请人提供）：自闭症谱系障碍（ASD）的特征是社会和非社会认知能力的明显障碍，这些障碍持续到成年，并导致严重的功能障碍。ASD的治疗几乎完全集中在儿童身上，很少有经验支持的干预措施可用于解决ASD患者在过渡到成年时面临的核心认知和功能挑战。认知康复已经成为一套系统的方法来补救认知障碍，有相当大的希望治疗自闭症的认知缺陷，但足够的动力和严格控制的研究，这些干预措施还没有在这个人群中进行。认知增强疗法（CET）是成人ASD最有前途的认知康复方法之一，因为它采用全面和发展的方法来针对神经认知和社会认知障碍，并且对精神分裂症（一种以类似认知为特征的疾病）具有既定的疗效。缺陷。在NIMH的支持下，我们最近证明了将CET适应于ASD成人的可行性，并且从我们在该人群中进行的CET的初始小规模随机试验中发现了证据，表明目标参与了不同的认知领域，对功能结果具有实质性的下游益处。令人兴奋的是，这些与CET相关的认知改善似乎也得到了额颞叶脑功能和连接的潜在神经可塑性变化的支持。这些证据表明，CET作为成人ASD的循证认知康复干预措施具有相当大的前景，并且这些早期发现是后续的足够动力的疗效试验。针对PA-13-216“自闭症谱系障碍研究”的心理社会干预重点，本项目拟在100名言语型成人ASD患者中进行CET的随机对照疗效试验。受试者将被随机分配至CET或强化支持治疗（EST）对照组，并接受18个月的治疗。该项目的具体目标是（1）评估CET与EST对不同认知和行为结果的比较有效性，以评估目标参与和功能影响，（2）检查CET对额颞叶内侧脑功能和连接的影响，以阐明该人群认知增强的神经机制，以及（3）使用个人和神经生物学指标来探索治疗反应的异质性，并确定最有可能从CET中获益的个体的调节因子。拟议的项目将导致成人ASD中最大的心理社会干预研究，以及第一个有足够动力的研究，为这一人群提供有前途的认知康复方法。如果成功，该项目将为ASD成年人提供干预措施迈出重要一步，并将展示成人ASD大脑的可塑性及其对认知康复的反应，为新一代自闭症治疗铺平道路。

 DESCRIPTION (provided by applicant): Autism spectrum disorder (ASD) is characterized by marked impairments in social and non-social cognitive ability that persist well into adulthood and contribute to significant functional disability. The treatment of ASD has focused almost exclusively on children, and few empirically supported interventions are available to address the core cognitive and functional challenges individuals with ASD face as they transition to adulthood. Cognitive rehabilitation has emerged as a set of systematic approaches to the remediation of cognitive impairments that hold considerable promise for the treatment of cognitive deficits in autism, yet adequately-powered and rigorously controlled studies of these interventions have not been conducted in this population. Cognitive Enhancement Therapy (CET) represents one of the most promising cognitive rehabilitation approaches for adult ASD due to its comprehensive and developmental approach to targeting neurocognitive and social-cognitive impairments as well as its established efficacy in schizophrenia, a disorder characterized by similar cognitive deficits. With support from NIMH, we have recently demonstrated the feasibility of adapting CET to adults with ASD, and evidence is emerging from our initial, small-scale randomized trial of CET in this population indicating target engagement on diverse areas of cognition with substantial downstream benefits to functional outcomes. Excitingly, these improvements in cognition associated with CET also appear to be supported by underlying neuroplastic changes in fronto-temporal brain function and connectivity. Such evidence suggests that CET has considerable promise as an evidence-based cognitive rehabilitation intervention for adult ASD, and it is critical that these early findings are followe-up with an adequately-powered efficacy trial. In response to the psychosocial intervention focus of PA-13-216, "Research on Autism Spectrum Disorders", this project proposes to conduct a randomized-controlled efficacy trial of CET in 100 verbal adults with ASD. Participants will be randomized to CET or an Enriched Supportive Therapy (EST) control condition and treated for 18 months. Specific aims of the project are to (1) evaluate the comparative effectiveness of CET versus EST on diverse cognitive and behavioral outcomes to assess target engagement and functional impact, (2) examine the effects of CET on fronto-medial temporal brain function and connectivity to elucidate the neural mechanisms of cognitive enhancement in this population, and (3) use personal and neurobiological indicators to explore heterogeneity in treatment response and identify moderators indicative of individuals most likely to benefit from CET. The proposed project will result in the largest psychosocial intervention study in adult ASD, and the first adequately-powered study of a promising cognitive rehabilitation approach for this population. If successful, this project will provide a major step forward in making interventions available for adults with ASD, and will demonstrate the plasticity of the adult ASD brain and its responsiveness to cognitive rehabilitation, paving the way for a new generation of treatments in autism.